Bret S. Stetka, MD


June 24, 2013

In This Article

What Interventions Work?

"The goal is to protect the healthy brain rather than repair a damaged brain," Small continued, moving on to prevention and treatment strategies, "and to develop disease-modifying drugs," noting that, unfortunately, currently available medications are primarily symptomatic. Still, drugs like donepezil, memantine, and rivastigmine do benefit patients and can slow clinical progression. "If you take patients off of the drug too early they will get worse faster," said Small. Medications that clear amyloid from the brain are thought to be a potential disease-modifying approach, one that has received a great deal of research attention. However, this work has yet to pan out. Studies are also underway looking at various other preventive strategies in AD, including anti-tau and anti-inflammatory treatments, cholesterol-lowering drugs, and an insulin nasal spray, developed as a result of the association between diabetes and AD.

Anti-inflammatory therapies may hold particular promise in slowing AD progression. A study by Small and colleagues from 2008[15] found that anti-inflammatory treatment increases cognition and brain function in normal aging; however, at the moment he doesn't recommend anti-inflammatories for brain health given the limited data and side effects.

The MacArthur Studies of Successful Aging[16] suggests that genetics may account for only a third of AD risk, with the rest dependent on nongenetic factors, suggesting a major role for lifestyle modification in preventing AD. Small spent the remainder of his talk reviewing the lifestyle factors thought to influence brain health and aging: (1) physical conditioning; (2) mental stimulation; (3) stress management; and (4) nutrition.


Of all lifestyle approaches that might contribute to AD prevention, the strongest evidence exists for exercise. Active animals have larger hippocampi, while older people who walk regularly -- even as little as 15 minutes a day -- have a lower risk for AD. People who routinely exercise exhibit better cognitive abilities and actually have larger brains. Regular exercise also results in lower PiB and FDDNP binding in the brain, reduced CSF tau, and increased CSF amyloid, all markers of decreased AD risk.[17]

Mental Stimulation

Read, write, and do a crossword: Mentally stimulating activities and certain brain-training programs are in the long term associated with lower brain amyloid levels and a decreased risk for AD, as are graduating from college or engaging in life-long learning.[18,19] However as Small pointed out, data such as these are caveated by the chicken or egg conundrum: "Are people with good brain genes more often going onto college, or is it the mental enrichment that [is effective]?" wondered Small. "I think it's probably a combination."

Many worry that our increasing reliance on technology hinders our mental stimulation -- that digital dependence will in fact hasten neurologic deterioration. Small cited a recent cover story in the Atlantic, "Is Google Making Us Stoopid [sic]." His group at UCLA set to find out. Their study, "Your Brain On Google,"[20] looked at brain activity in Internet-naive research volunteers, people who had literally never used the Internet. "They were hard to find, and I quickly learned that I could not recruit them online," joked Small.

Using functional MRI, his research team compared brain activity in the internet-naive with Internet-experienced controls when each was asked to search online vs reading information from a book. The Internet-naive subjects had minimal activity in expected brain regions when reading a book and similar brain activity when searching online for the first time. When the Internet-savvy people searched online, there was a 2-fold increase in activity throughout the brain compared with interpreting a book and compared with the Internet-naive volunteers. And after just a week of searching online, the Internet-naive subjects demonstrated significant increases in brain activity in areas responsible for working memory and decision-making, likely due to the decision-making and engagement required to navigate the Internet. At least in this case, engaging with technology actually increased mental stimulation. However, like many tasks, once one gets more proficient at searching online, activity decreases as the brain becomes more efficient at the activity.

Small and colleagues use a number of mental stimulation and compensatory techniques at UCLA's Longevity Center. Their memory fitness programs and brain boot camps can be licensed out for use and show significant effects on memory and brain efficiency. A simpler approach recommended by Small is called "Look, Snap, Connect," which encourages patients to take "mental snapshots" and create meaningful associations. Among his series of examples was an attorney named Sue Bangal -- "She has bangs and could 'sue' me." It might sound silly, but it works. He then flashed 8 words and asked the audience to create a visual story in their head to help remember them: beach, professor, horse, teddy bear, cigar, nun, palm tree, and pasta.


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